Intrabody surgical fluid transfer assemblies with adjustable exposed cannula to needle tip length, related systems and methods

ABSTRACT

Devices for transferring fluid to or from a subject include an elongate tubular cannula having opposing proximal and distal ends with an axially extending lumen. The devices also include an elongate needle having opposing proximal and distal ends. The elongate needle is configured so that the distal end of the needle extends out of the distal end of the cannula a suitable adjustable distance. The devices also include a housing with a length adjustment mechanism that adjusts a length between the tip of the needle and the distal end of the tubular cannula.

RELATED APPLICATIONS

This application claims the benefit of and priority to U.S. ProvisionalApplication Ser. No. 62/296,323, filed Feb. 17, 2016, and U.S.Provisional Application Ser. No. 62/382,434, filed Sep. 1, 2016, thecontents of which are hereby incorporated by reference as if recited inentirety herein.

FIELD OF THE INVENTION

The present invention relates generally to medical devices and systemsand, more particularly, to devices and systems for delivering and/orwithdrawing substances in vivo.

BACKGROUND

Various therapeutic and diagnostic procedures require that a substancebe delivered (e.g., infused) into a prescribed region of a patient, suchas to an intrabody target using a delivery device. It may be importantor critical that the substance be delivered with accuracy to the targetregion in the patient and without undue trauma to the patient.

SUMMARY

It should be appreciated that this Summary is provided to introduce aselection of concepts in a simplified form, the concepts being furtherdescribed below in the Detailed Description. This Summary is notintended to identify key features or essential features of thisdisclosure, nor is it intended to limit the scope of the invention.

Embodiments of the invention are directed to intrabody fluid transferassemblies with adjustable exposed tubular cannula to needle tip length,related systems and methods.

Embodiments of the invention are directed to a surgical device fortransferring fluid to or from a subject. The device includes a tubularcannula (which may be referred to as an elongate guide cannula) havingopposing proximal and distal ends with an open axially extending lumen.The device also includes an elongate needle (which can also be referredto as a “capillary” or “capillary tube”) having opposing proximal anddistal ends. The elongate needle is configured to extend through(typically slidably insertable into) the tubular cannula lumen so thatthe distal end of the needle extends a distance out of the distal end ofthe tubular cannula. The device also includes a length adjustmenthousing for positional adjustment of length between the distal end ofthe tubular cannula and the exposed tip of the needle.

The tubular cannula and/or needle can be held in the housing to beretracted and extended from the housing.

The length adjustment housing can reside external of a patient when thedistal end portion of the tubular cannula and needle are in the patient.

The housing can rotate in a defined direction to extend at least one ofthe needle or the cannula.

A portion of the needle resides in and/or is attached to or attachableto a length of flexible tubing. The elongate needle can be formed offused silica glass. The distal end of the needle can have a steppedconfiguration with a first segment having a first outer diameter thatmerges into a second end segment having a second smaller outer diameter,the second segment having a length that extends to a tip of the needle.

The needle may comprise an inner capillary member and an outer capillarymember of a larger diameter than the inner capillary tube but a smallerdiameter than the cannula tube.

The outer capillary tube can comprise a shrink fit sleeve to sealablyengage the inner wall of the lumen of the tubular cannula.

The distance that the needle tip extends out of the distal end of thetubular cannula is between about 2 mm to about 30 mm and this length canbe extended or retracted relative to the tubular cannula when thetubular cannula and needle tip are in the body of a patient (i.e., abrain).

The tubular cannula can be formed of and/or include a ceramic material.

The tubular cannula can have an outer polymeric coating and/or sleeve.

The distal end of the tubular cannula can be tapered so that it has asmaller outer diameter at a tip relative to an outer diameter of thetubular cannula more proximal or rearward of the tapered distal end.

The elongate needle can be an infusate needle that has a stepped distalend configuration and is integrally attached to the flexible tubing as asubassembly.

The needle and tubular cannula can be MRI compatible for use in an MRIguided procedure.

The intrabody devices can be particularly suitable forwithdrawing/introducing fluid from/into the ventricular brain.

The tubular cannula can be formed of or include a ceramic material.

The tubular cannula can have an outer polymeric coating and/or sleeve.

The distal end of the tubular cannula can be tapered so that it has asmaller outer diameter at a tip relative to an outer diameter of thetubular cannula at a more medial or proximal portion and/or rearward ofthe tapered distal end.

The tubular cannula can be formed of and/or include a ceramic material.

The tubular cannula and the outer capillary can each comprise aconformal outer polymeric sleeve.

The distal end portion of the needle that extends out of the tubularcannula can have at least first and second co-axially disposed segmentshaving different outer diameters, with a smallest sized outer diameterof the first segment extending to a tip thereof.

The tubular cannula can have an exterior surface on a distal end portionthereof that tapers down in size to a tip thereof to define a thirdcoaxially disposed stepped segment that resides a distance rearward ofthe second segment and has a larger outer diameter than both the firstand second co-axially disposed segments.

The needle can have a fused glass silica body.

An outer surface of the tubular cannula can have a size and geometryadapted for use with a stereotactic frame.

The needle can have an inner diameter of between about 100 μm to about750 μm.

The first smallest outer diameter segment can have a longitudinal lengthof between about 1 mm to about 10 mm. The second segment can have alongitudinal length of between about 2 mm to about 20 mm. The distal tipof the guide cannula can reside a distance between 3 mm to about 30 mmfrom a distal tip of the needle.

Yet other embodiments are directed to methods of transferring asubstance to and/or from a patient, the methods include: providing atubular cannula with an axially extending interior lumen and a needlehaving an internal lumen with a distal end of the needle extending outof the tubular cannula at a target site; then transferring the substanceto or from the target site through the needle lumen.

The needle can be an infusion needle. The transferring the substance toor from the target site can be carried out by infusing a substance intotarget tissue such as into the brain or into the heart, for example.

It is noted that aspects of the invention described with respect to oneembodiment may be incorporated in a different embodiment although notspecifically described relative thereto. That is, all embodiments and/orfeatures of any embodiment can be combined in any way and/orcombination. Applicant reserves the right to change any originally filedclaim or file any new claim accordingly, including the right to be ableto amend any originally filed claim to depend from and/or incorporateany feature of any other claim although not originally claimed in thatmanner. These and other objects and/or aspects of the present inventionare explained in detail below.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1A is a side view of an exemplary intrabody fluid transfer assemblyshown in an exemplary first position according to embodiments of thepresent invention.

FIG. 1B is a side view of the exemplary intrabody fluid transferassembly shown in an exemplary second position, with the needle tipfurther away from a distal end of the tubular cannula than in the firstposition, according to embodiments of the present invention.

FIG. 2A is a side view of the assembly shown in FIG. 1A in the firstposition.

FIG. 2B is a section view taken along lines 2B-2B in FIG. 2A accordingto embodiments of the present invention.

FIG. 3A is a side view of the assembly shown in FIG. 1B in the secondposition.

FIG. 3B is a section view taken along lines 3B-3B in FIG. 3A accordingto embodiments of the present invention.

FIG. 4A is a side view of some components of the assembly shown in FIG.1B.

FIG. 4B is a partial exploded view of the components shown in FIG. 4Aaccording to embodiments of the present invention.

FIG. 5A is a side view of the assembly shown in FIG. 1B in the secondposition according to embodiments of the present invention.

FIG. 5B is a section view taken along lines 5B-5B in FIG. 5A of theassembly shown in FIG. 5A.

FIG. 5C is a section view taken along lines 5C-5C in FIG. 5A.

FIG. 6 is an enlarged section view of components of the assembly shownin FIG. 5A according to some embodiments of the present invention.

FIG. 7 is a greatly enlarged side perspective view of a housing of anassembly with a length adjustment mechanism/mechanism according toembodiments of the present invention.

FIG. 8A is a side perspective view of another embodiment of an intrabodyfluid transfer assembly according to embodiments of the presentinvention.

FIG. 8B is a side perspective view of the assembly shown in FIG. 8A butillustrating the exposed needle tip further extended according toembodiments of the present invention.

FIG. 9A is a greatly enlarged partially transparent view of the housingassembly shown in FIGS. 8A and 8B.

FIG. 9B is a greatly enlarged partially transparent view of anotherembodiment of a housing for the assembly shown in FIGS. 8A and 8Baccording to embodiments of the present invention.

FIG. 9C is a side partially exposed view of the infusion assembly shownin FIG. 9B illustrating a needle tip to tubular cannula retractedconfiguration with the gear outside the housing according to embodimentsof the present invention.

FIG. 9D is a side partially exposed view of the infusion assembly shownin FIG. 9C illustrating a needle tip to tubular cannula extendedconfiguration with the gear inside the housing according to embodimentsof the present invention.

FIG. 9E is a top view with the housing shown partially transparent ofthe transfer assembly shown in FIG. 9C.

FIG. 9F is a section view taken along line 9F-9F in FIG. 9E.

FIGS. 9G, 9H and 9I illustrate exemplary attachment regions of variouscomponents of the fluid transfer assembly shown in FIGS. 9D and 9Eaccording to embodiments of the present invention.

FIG. 10A is a side perspective view of another embodiment of anintrabody fluid transfer assembly according to embodiments of thepresent invention.

FIG. 10B is a side perspective view of the assembly shown in FIG. 10Abut illustrating the exposed needle tip further extended according toembodiments of the present invention.

FIG. 11A is a side perspective, partially exploded view of the intrabodyfluid transfer assembly shown in FIG. 10A.

FIG. 11B is a greatly enlarged partial assembly view of the portion ofthe intrabody fluid transfer assembly shown in FIG. 11A.

FIG. 12A is a side partially exposed view of the infusion assembly shownin FIG. 10A illustrating a needle tip to tubular cannula retractedconfiguration with the gear outside the housing according to embodimentsof the present invention.

FIG. 12B is a side partially exposed view of the infusion assembly shownin FIG. 12A illustrating a needle tip to tubular cannula extendedconfiguration with the gear inside the housing according to embodimentsof the present invention.

FIG. 12C is a top view with the housing shown partially transparent ofthe transfer assembly shown in FIG. 9C.

FIG. 12D is a section view taken along line 12D-12D in FIG. 12C.

FIGS. 12E and 12F illustrate exemplary attachment regions of variouscomponents of the fluid transfer assembly shown in FIGS. 12A-12Daccording to embodiments of the present invention.

FIG. 13 is a top view of an exemplary intrabody fluid transfer assemblyaccording to embodiments of the present invention.

FIG. 14 is a schematic illustration of an MRI-guided interventionalsystem in which embodiments of the present invention may be utilized.

FIG. 15 is a sectional view of the trajectory guide of the MRI-guidedsystem of FIG. 14 with an exemplary needle and surgical cannula fortransferring a substance (e.g., an infusate, etc.) to an intrabodytarget region of a patient.

FIG. 16 is a flow chart of exemplary actions that can be carried outaccording to embodiments of the present invention.

DETAILED DESCRIPTION

The present invention now is described more fully hereinafter withreference to the accompanying drawings, in which some embodiments of theinvention are shown. This invention may, however, be embodied in manydifferent forms and should not be construed as limited to theembodiments set forth herein; rather, these embodiments are provided sothat this disclosure will be thorough and complete, and will fullyconvey the scope of the invention to those skilled in the art.

Like numbers refer to like elements throughout. In the figures, thethickness of certain lines, layers, components, elements or features maybe exaggerated for clarity. The terms “FIG.” and “Fig.” are usedinterchangeably with the word “Figure” in the specification and/orfigures.

The terminology used herein is for the purpose of describing particularembodiments only and is not intended to be limiting of the invention. Asused herein, the singular forms “a”, “an” and “the” are intended toinclude the plural forms as well, unless the context clearly indicatesotherwise. It will be further understood that the terms “comprises”and/or “comprising,” when used in this specification, specify thepresence of stated features, steps, operations, elements, and/orcomponents, but do not preclude the presence or addition of one or moreother features, steps, operations, elements, components, and/or groupsthereof. As used herein, the term “and/or” includes any and allcombinations of one or more of the associated listed items.

Unless otherwise defined, all terms (including technical and scientificterms) used herein have the same meaning as commonly understood by oneof ordinary skill in the art to which this invention belongs. It will befurther understood that terms, such as those defined in commonly useddictionaries, should be interpreted as having a meaning that isconsistent with their meaning in the context of the specification andrelevant art and should not be interpreted in an idealized or overlyformal sense unless expressly so defined herein. Well-known functions orconstructions may not be described in detail for brevity and/or clarity.

It will be understood that when an element is referred to as being “on”,“attached” to, “connected” to, “coupled” with, “contacting”, etc.,another element, it can be directly on, attached to, connected to,coupled with or contacting the other element or intervening elements mayalso be present. In contrast, when an element is referred to as being,for example, “directly on”, “directly attached” to, “directly connected”to, “directly coupled” with or “directly contacting” another element,there are no intervening elements present. It will also be appreciatedby those of skill in the art that references to a structure or featurethat is disposed “adjacent” another feature may have portions thatoverlap or underlie the adjacent feature.

Spatially relative terms, such as “under,” “below,” “lower,” “over,”“upper” and the like, may be used herein for ease of description todescribe one element or feature's relationship to another element(s) orfeature(s) as illustrated in the figures. It will be understood that thespatially relative terms are intended to encompass differentorientations of the device in use or operation in addition to theorientation depicted in the figures. For example, if the device in thefigures is inverted, elements described as “under” or “beneath” otherelements or features would then be oriented “over” the other elements orfeatures. Thus, the exemplary term “under” can encompass both anorientation of “over” and “under”. The device may be otherwise oriented(rotated 90 degrees or at other orientations) and the spatially relativedescriptors used herein interpreted accordingly. Similarly, the terms“upwardly,” “downwardly,” “vertical,” “horizontal” and the like are usedherein for the purpose of explanation only unless specifically indicatedotherwise.

The term “about,” as used herein with respect to a value or number,means that the value or number can vary by +/−twenty percent (20%).

The term “monolithic” means that the component (e.g., needle) is formedof a single uniform material.

The term “MRI visible” means that a device is visible, directly orindirectly, in an MRI image. The visibility may be indicated by theincreased SNR of the MRI signal proximate to the device (the device canact as an MRI receive antenna to collect signal from local tissue)and/or that the device actually generates MRI signal itself, such as viasuitable hydro-based coatings and/or fluid (typically aqueous solutions)filled channels or lumens.

The term “MRI compatible” means that a device is safe for use in an MRIenvironment and/or can operate as intended in an MRI environment withoutgenerating MR signal artifacts, and, as such, if residing within thehigh-field strength region of the magnetic field, is typically made of anon-ferromagnetic MRI compatible material(s) suitable to reside and/oroperate in a high magnetic field environment.

The term “high-magnetic field” refers to field strengths above about0.5T (Tesla), typically above 1.0T, and more typically between about1.5T and 10T.

The term “near real time” refers to both low latency and high framerate. Latency is generally measured as the time from when an eventoccurs to display of the event (total processing time). For tracking,the frame rate can range from between about 100 fps to the imaging framerate. In some embodiments, the tracking is updated at the imaging framerate. For near “real-time” imaging, the frame rate is typically betweenabout 1 fps to about 20 fps, and in some embodiments, between about 3fps to about 7 fps. The low latency required to be considered “near realtime” is generally less than or equal to about 1 second. In someembodiments, the latency for tracking information is about 0.01 s, andtypically between about 0.25-0.5 s when interleaved with imaging data.Thus, with respect to tracking, visualizations with the location,orientation and/or configuration of a known intrabody device can beupdated with low latency between about 1 fps to about 100 fps. Withrespect to imaging, visualizations using near real time MR image datacan be presented with a low latency, typically within between about 0.01ms to less than about 1 second, and with a frame rate that is typicallybetween about 1-20 fps. Together, the system can use the tracking signaland image signal data to dynamically present anatomy and one or moreintrabody devices in the visualization in near real-time. In someembodiments, the tracking signal data is obtained and the associatedspatial coordinates are determined while the MR image data is obtainedand the resultant visualization(s) with the intrabody device (e.g.,stylet) and the near RT MR image(s) are generated.

The term “sterile,” as used herein, means that a device, kit, and/orpackaging meets or exceeds medical/surgical cleanliness guidelines, andtypically is free from live bacteria or other microorganisms.

Embodiments of the present invention can be utilized with variousdiagnostic or interventional devices and/or therapies to any desiredinternal region of an object using any suitable imaging modality,typically an MRI and/or in an MRI scanner or MRI interventional suite.However, CT or other imaging modalities may be used. The object can beany object, and may be particularly suitable for animal and/or humansubjects for e.g., animal studies and/or veterinarian or humantreatments. Some embodiments deliver therapies to the spine. Someembodiments deliver therapies to treat or stimulate a desired region ofthe sympathetic nerve chain. Other uses, inside or outside the brain,nervous system or spinal cord, include stem cell placement, gene therapyor drug delivery for treating physiological conditions, chemotherapy,drugs including replicating therapy drugs. Some embodiments can be usedto treat tumors.

The term “substance,” as used herein, refers to a liquid for treating orfacilitating diagnosis of a condition and can include bions, stem cellsor other target cells to site-specific regions in the body, such asneurological, nerves or other target sites and the like. In someembodiments, stem cells and/or other rebuilding cells or products can bedelivered into spine, brain or cardiac tissue, such as a heart wall viaa minimally invasive MRI guided procedure, while the heart is beating(i.e., not requiring a non-beating heart with the patient on aheart-lung machine). Examples of known stimulation treatments and/ortarget body regions are described in U.S. Pat. Nos. 6,708,064;6,438,423; 6,356,786; 6,526,318; 6,405,079; 6,167,311; 6,539,263;6,609,030 and 6,050,992, the contents of which are hereby incorporatedby reference as if recited in full herein.

The term “infusion” and derivatives thereof refers to the delivery of asubstance (which can be a single substance or a mixture) at a relativelyslow rate so that the substance can infuse about a target region. Thus,the term “infusate” refers to a substance so delivered.

Embodiments of the present invention will now be described in furtherdetail below with reference to the figures. FIGS. 1A and 1B illustratean exemplary intrabody fluid transfer assembly 10 with a tubular cannula20, a needle 30 and a housing 40 with a length adjustment mechanism 50attached (directly or indirectly) to one or both of the tubular cannula20 and needle 30 to be able to extend and retract one or both relativeto the distal end 40 d of the housing. The term “needle” refers to arelatively small device with an open lumen (30 l, FIG. 5C) extending toits tip 30 t to release or intake fluid.

The tubular cannula 20 can comprise a different material than the needle30. Where the needle 30 comprises inner and outer capillary tubes 31,33, the outer capillary tube 33 can be shorter than the inner capillarytube 31 and may terminate inside the housing 40. By way of example only,the tubular cannula 20 can be a ceramic tube that has increased rigidityrelative to the needle and the needle 30 can be formed of fused silica.

The length adjustment mechanism 50 is configured to adjust a distance orlength D₁ between the distal end 20 d of the tubular cannula and theexposed tip 30 t of the needle. The length adjustment mechanism 50 canbe configured to provide a maximal stroke length of between 0.5 inchesand 3 inches, more typically between about 0.75 inches to about 1 inch(2.5 cm) such as about 0.79 inches. The length adjustment can be carriedout in vivo while the housing remains external of a patient with thedistal end of the cannula 20 d and needle tip 30 t in the body of thepatient.

The distal end of the housing 40 d can reside at a distance that isbetween 4-10 inches from the needle tip 30 t, more typically between 4and 5 inches. This length can remain fixed in some embodiments.

The needle 30 may comprise an inner capillary tube 31 with a lengthsufficient to define the tip 30 t and may have an outer capillary tube33 that resides a distance rearward from the tip 30 t to form at leastone stepped distal end portion 30 s (so that the needle 30 merges from alarger diameter to a smaller diameter at a distal end portion thereof,toward the tip 30 t) of the needle 30. This stepped portion can define asurface that is orthogonal to the cannula/needle axis.

As shown in FIGS. 1A and 1B, the tubular cannula 20 can have opposingproximal and distal ends 20 p, 20 d, respectively. The tubular cannula20 can have an external exposed stepped and/or tapered segment 21 (theouter diameter becoming smaller in a direction of the needle tip 30 t).The distance between the distal end of the tubular cannula 20 d and theneedle tip 30 t can be adjusted by a user to position the taperedsegment 21 closer or further away from the needle tip 30 t.

As shown in FIGS. 1A, 2A and 2B, for example, in a first configuration,the needle tip 30 t resides at a short distance “D₁” from the distal endof the cannula 20 d while in FIG. 1B, in a second configuration, thedistal end of the cannula 20 d resides at a longer distance D₂ from theneedle tip 30 t. D₂ can be between about 0.5 inches and about 3 inches,more typically between about 0.5 inches and about 1.1 inch. D₁ can bebetween about 1 mm to about 50 mm, typically between 1 mm and 10 mm, andin some embodiments between about 2 mm to about 4 mm, such as about 3mm.

The needle tip 30 t may be configured to reside at a fixed extendedlength from the distal end 20 d of the housing which may be betweenabout 4 and 6 inches, more typically between about 4.8 and about 5inches, in some particular embodiments.

In some particular embodiments, the distal end of the tubular cannula 20d can reside at a length L₂ that is about 4.7 inches in a fully extendedposition (FIG. 1A) and at about 3.93 inches in a fully retractedposition (FIG. 1B). However, other stroke distances and extended andretracted lengths may be used.

Referring to FIG. 1B, the distal end portion of the needle 30 d can haveat least one stepped segment 30 s that can have an increased outerdiameter relative to the tip 30 t. The stepped segment 30 s can residein the distal end of the cannula 20 d in the configuration shown inFIGS. 1A, 2A and 2B.

The stepped segment 30 s can reside a fixed length D1 from the tip 30 t.D₁ can be, for example, between about 1 mm to about 50 mm, typicallybetween 1 mm and 10 mm, and in some embodiments between about 2 mm toabout 4 mm, such as about 3 mm. In the configuration shown in FIG. 1B,for example, the needle 30 can have an exposed length L₃ that extendsrearward from the stepped segment 30 s with the increased outer diameterout of the distal end of the tubular cannula 20 d. L₃ can be longer thanD₁ and can be between about 2 mm and 20 mm. The distal end portion ofthe needle 30 d may include more than two co-axially aligned(concentric) stepped segments 30 s.

The tubular cannula 20 can have a length L₂ that extends out of thehousing 40 that varies to provide the positional adjustment relative tothe tip. In other embodiments, the tubular cannula 20 can remain fixedin position in the housing 40 and the needle 30 can be extended andretracted relative to the housing 40. In yet other embodiments, thetubular cannula 20 and the needle 30 can each be extendable andretractable out of the distal end of the housing 40 d.

The length D₂ of the distal end portion of the needle 30 outside thecannula 20 during delivery can be between about 3 mm to 30 mm. Theselengths can be selected to inhibit reflux and/or provide a desireddelivery path during infusion.

The needle 30 can have a stepped distal end portion that cooperates withthe cannula 20 to form co-axially disposed step segments (theorthogonally extending end face at the distal end 20 d of the cannula,and the stepped segment 30 s of the needle. There can be three differentouter diameters that are longitudinally separated with steps on one ormore of end faces S₁, S₂, S₃ (FIG. 4A). One or some of the steps S₁, S₂,S₃ can serve to reduce or prevent reflux of the delivered substance. Theend face at taper segment S₃ can be a conical face rather than anorthogonal end face provided at S₁ and S₂ (orthogonal to the axialdirection of the needle axial direction and the tubular cannula axialdirection).

According to some embodiments, the inner diameter of the needle 30 is inthe range of from about 10 μm to 1 mm and, in some particularembodiments, is between about 100 μm to about 750 μm, such as about 200μm. According to some embodiments, the outer diameter at the tip 30 t isin the range of from about 75 μm to 1.08 mm and, in some embodiments, isabout 360 μm.

In some embodiments, as shown in FIGS. 1A and 1B, for example, an outerwall 40 w of the housing 40 can be (manually or electro-mechanically)rotated in a first direction (indicated by the arrow with the letter“R”) to retract the length adjustment mechanism 50 in the housing 40,which, in turn, exposes a larger length of the distal end of the needle30 (FIGS. 1B, 3A, 3B). The rotation can be in either direction for theretraction and is typically manually carried out. The rotation of theouter wall of the housing 40 w can retract the tubular cannula 20 and/orextend the needle 30.

The rotatable outer wall 40 w can be the entire outer wall or a portionof the outerwall. The rotatable outer wall 40 w can be between about 1about 6 inches long and may have a small diameter, greater than thediameter of the outer wall of the tubular cannula 20 and less than about0.3 inches, in some embodiments. The rotatable outer wall 40 w can becylindrical.

According to some embodiments, at least part of an exposed length of thetubular cannula 20 has an outer surface comprising a polymeric supportsleeve 23 (FIG. 3A) which can comprise a shrink tube and may have athickness in the range of from about 40 μm to about 60 μm.

While different sizes may be appropriate for different uses, the tubularcannula 20 can, in some embodiments, have an outer diameter that isbetween about 0.2 inches and 0.015 inches, such as, in some particularembodiments about 0.061 inches and an inner diameter that is between0.10 inches and 0.001 inches, such as, in some particular embodiments,about 0.029 inches. The tubular cannula 20 can have a lower portion witha smaller outer diameter than an upper or proximal portion or may have aconstant outer diameter over its length to the tapered segment 21.

The needle 30 can be fused silica and may also include an outer wallcovered by a sleeve 35 which can comprise a shrink tube or otherpolymeric sleeve or coating, typically starting at the stepped segment30 s and extending a length over the outer capillary 33 as shown, forexample in FIGS. 3A and 5C, to facilitate a suitably fluid-tightinterface at the distal end of the tubular guide cannula 20 d to inhibitor reduce fluid entry into this interface/space during delivery orintake. The sleeve 35 can be polyester and can have a thickness that isbetween about 0.00125 inches and 0.00150 inches (0.032-0.038 mm), insome embodiments.

As shown in FIGS. 1A, 1B, 2A and 2B, for example, the assembly 10 canhave a connector 60, such as a female or male luer connector (shown asfemale) that resides a distance away from the housing 40, typically alength that positions an upper/outer end 60 e a distance between 3-20inches away from the proximal end of the housing 40 p, more typicallybetween about 6-10 inches. The needle 30 (typically only the innercapillary 31 without the outer capillary 33, where used) can extendthrough the housing 40 to an internal portion of the connector 60 to bein fluid communication with the connector 60. Tubing 65, such as PVCtubing, can extend between a proximal end of the housing 40 p to theconnector 60 about the needle 30. The needle 30 can have a total lengthbetween the connector 60 and tip 30 t that can be at between about 10-20inches, typically about 15.65 inches.

Referring to FIGS. 3A, 3B, 4A and 4B, in some embodiments, the lengthadjustment mechanism 50 can comprise a longitudinally extending screw 50s that resides in the housing 40 and that can controllably translate inan axial direction to provide the positional adjustment of the distancebetween the distal end of the tubular cannula 20 d and the needle tip 30t. However, it is contemplated that other length adjustment mechanismsmay be used, such as, for example, gears such as worm gears, planetarygears, rack and pinions and the like, cams, ratchets, frictional slides,and/or linkages.

The housing 40 can include an internal, longitudinally extendingthreaded segment 40 t that engages threads 50 t of the length adjustmentscrew member 50 s. Thus, the outer wall of the housing 40 w can rotateand act as a nut to be able to threadably engage and rotate the screw 50s. The screw 50 s can have a relatively fine pitch configuration, suchas a thread configuration of 3-48 (48 threads per inch). The screw 50 scan be of brass for MRI compatibility, but other materials may be usedas well as other pitch configurations.

In the embodiment shown in FIGS. 2B, 3A and 3B, for example, an outerwall 20 w of the tubular cannula can be fixably attached to the screw 50s, typically bonded, so that the threads form the outerwall of a portionof the tubular cannula 20 w (typically a proximal end portion of thecannula 20 p) but other fixation configurations may be used.

In some embodiments, the outerwall of the tubular cannula 20 w can havethe thread pattern formed directly therein. In some embodiments, theneedle 30 can be fixably attached to the screw 50 s (not shown) to allowlength adjustment. In some embodiments, more than one internal screw canbe used, one attached to the tubular cannula 20 and one attached to theneedle 30 and separate portions of the housing 40 or members held by thehousing 40 can be used to selectively move each of the cannula 20 andthe needle 30 to provide adjustable exposed lengths (not shown).

Referring to FIGS. 2B, 3B, 4A and 4B, the housing 40 can have an axiallyextending lumen 41 and an inner, longitudinally extending wall orsurface 41 s extending about the lumen, at least a longitudinallyextending segment of which can be threaded 40 t, typically for asub-length of the overall length of the housing 40 residing between theproximal and distal ends of the housing. The threads 40 t can beconfigured to define hard stops at fully retracted and fully extendedpositions which can be associated with a short linear distance ofbetween about 0.5 inches and 1.25 inches.

The housing 40 can be manually held by a finger(s) or hand of a userduring use to allow for manual rotation of the housing outer wall 40 wor other user input to the screw 50 s or may be supported by a supportframe or member (not shown).

The device 10 may also include a handle body 70 held in the housing 40that has a longitudinally extending slot 72 that allows a laterallyextending pin 55 attached to the screw 50 s and/or tubular cannula 20 inthe embodiment shown, to move therein. The handle body 70 and/or outersurface of the housing 40 thereat can include visual indicia of position77 such as symmetrically spaced apart marks and/or a graduated scale,for example. The pin 55 can include a color-contrast segment 55 c (FIG.7) that extends across the slot 72 at or above an outer surface of awall at the slot 72 to align with aligned spaced apart visual indiciamarks 77 across the slot to facilitate visual recognition of theextended or retracted length position (distance between the needle tip30 t and distal end of the guide cannula 20 d).

The handle body 70 can have an elongate cylindrical shape with anaxially extending interior cavity surrounding the tubular cannula 20 andmay be encased in the housing 40. The housing 40 can have a transparentor visually transmissive outer wall 40 w. The handle body 70 can have aproximal end 70 p that resides in the housing 40, typically abutting aledge forming a pocket 40 k (FIGS. 2B, 3B) and a larger distal end 70 dthat defines the distal end of the housing 40 d allowing the tubularcannula 20 to extend therethrough when assembled (FIGS. 2A, 2B, 3A and3B, for example).

In some embodiments, the handle body 70 can provide some or all of theinternal threads 40 t that cooperate with the screw 50 s. In someembodiments, the handle body 70 is devoid of internal threads and merelyallows the tubular cannula 20 and/or threaded member 50 s tolongitudinally (slidably) translate closely spaced thereto in the cavityof the handle body 70.

The handle body 70 can be attached to an innerwall 40 i of the housing(FIGS. 2B, 3B) and/or may be held in the pocket 40 k (FIG. 2B) extendingbetween a medial to a distal end portion of the housing 40. A supportmember 44 can be affixed to a distal end of the housing 40 d to lock thehandle body 70 in position while allowing the lower end portion of thetubular cannula 20 to extend out from the housing. The handle body 70can be static and can allow the pin 55 to move up and down along theslot 72 to inhibit rotation of the handle body 70 during rotation of thescrew 50 s.

A proximal support member 47 can be attached at a top of the housing 40.The proximal support member 47 can have a small rigid tubular projectionthat attaches to the flex tubing 65 that extends a distance such asbetween 1-10 inches, typically about 3-8 inches, between the supportmember 47 and connector 60. In other embodiments, the connector 60 canbe directly attached to the end member 47 and/or housing 40 (not shown).

The support end members 44, 47 and the handle body 70 can all remainstationary during use as the outerwall 40 w is rotated. The end supportmembers 44, 47 can capture the housing 40 therebetween, which can rotatein response to a user's direction clockwise and or counterclockwise tocause the translation and adjust the needle tip 30 t to the distal endof the cannula 20 length. Thus, the wall of the housing 40 and the screw50 s can rotate to move the tubular cannula 20 (as shown) and/or theneedle 30 (not shown).

The outer wall of the housing 40 w can include an elongate bracket 42(FIGS. 2B, 4B) that is adjacent but laterally spaced apart from therotatable outer wall 40 w and can be attached to each end member 44, 47.

Referring now to FIGS. 3A, 3B, 5A, 5B, 5C and 6, for example, and insome exemplary embodiments, the needle 30 can comprise the innercapillary tube 31 and the outer capillary tube 33 and the tubes 31, 33can be fixably attached, typically bonded together, so that they have afixed configuration relative to each other such that the inner capillary31 extends about 3 mm from the distal end of the outer capillary 33. Anexternal polymeric conformable tube (i.e., a polyester shrink wrap tube)35 can reside over the outer capillary tube 33 at least for a distancethat can be external of the housing and/or distal end of the cannula 20d.

The length adjustment mechanism 50 can be fixably attached (typicallybonded) to the needle 30 or the tubular cannula 20. The externalpolymeric conformable tube (i.e., a shrink wrap tube) 23 can reside overan exposed length of the cannula 20, typically over a distal end thereof20 d with the tapered end 21. The pin 55 can also be attached (i.e.,bonded) to the screw 50 s and/or tubular cannula 20. The screw 50 s canbe affixed to a proximal end portion of the tubular cannula 20 p,typically for a length between about 0.5 inches and 2 inches, moretypically between about 0.75 inches and 1.1 inches, in some embodiments.The tubular cannula 20 and outer capillary 33 can terminate inside thehousing 40, typically adjacent the proximal end 70 p of the handlebody). The upper end support 47 can be fixably attached (i.e., bonded)to the housing proximal end 40 p and the support tube 65 can be affixedto the end support 47. The end support member 44 can be affixed (i.e.,bonded) to the distal end portion of the handle body 70 d. The supporttube 65 with inner capillary tube 31 can also be fixably attached (i.e.,bonded) to the connector 60.

Referring to FIGS. 8A, 8B, 9A and 9B, the assembly 10′ can have a lengthadjustment mechanism 50′ that can include an external user interfacemember 50 i (shown as a thumbwheel) that extends laterally outward adistance beyond the housing 40 that is attached to the housing 40. Asshown, this mechanism 50′ includes a pinion gear 151 that engages alongitudinally extending internal rack gear 150 inside the housing 40.FIG. 8A illustrates a retracted configuration of the needle tip 30 t andFIG. 8B illustrates an exemplary extended position of the needle tip 30t relative to the distal end 20 d of the tubular cannula 20. Thus, theouter wall 40 w is not required to rotate. The rack gear 150 can bebonded or otherwise fixedly attached to the needle 30 (typically theinner capillary tube 31). The tubular cannula 20 can be rigid and heldby a distal end 40 d of the housing 40 to have a fixed length (i.e., itdoes not move).

Referring to FIGS. 9A and 9B, the rack gear 150 can have longitudinallyextending gear teeth 150 g on one side that face the pinion gear 151 andcan have a series of longitudinally spaced apart recesses 150 r (shownas arcuate recesses) along a length of the other opposing longitudinallyextending side that can slidably engage a pin 144 extending laterallyinside a cavity 140 c provided by mating first and second housingmembers 40 a, 40 b. The housing members 40 a, 40 b can include alongitudinally extending slot 141 that cooperate to hold the rack gear150 in position. The rack gear 150 can pull the needle 30 up and downrelative to the housing and the tubular cannula 20 to adjust theposition of the exposed needle tip 30 t. The rack gear 150 canoptionally include alignment tabs 153 that can engage alignment slots145 in the inner wall of one or both of the housing members 40 a, 40 b.

The rack gear 150 can be flexible (meaning it can be compressed or bentside to side or front to back using a small bending force or pressure).The rack gear 150 can have sufficient rigidity to have a self-supportingthree dimensional shape but can flex in any direction when outside thehousing 40. FIG. 9C illustrates by the arrows above the gear with anexemplary flex axis A, that the gear 150 can bend side to side relativeto the housing 40 when extended from the housing 40 with the needle 30(typically inner capillary 31) extending out each longitudinallyextending end thereof. The rack gear 150 can comprise a polymer such asa nylon or polycarbonate and may be injection molded.

As shown by the broken line extension 30 f of the needle in FIG. 8A, theextension of the needle 30 can be flexible and can loop and/or bend whenheld loose and not supported by a support member. The pinion gear 151may also be flexible or may comprise a different material than the rackgear and may be rigid, semi-rigid or be less flexible than the rack gear150.

FIGS. 8A, 8B and 9A illustrate that the housing 40 can curve (bearcuate, concave or convex) typically having a straight segment that canoptionally curve above the external length adjustment mechanism 50′and/or pinion gear 151. The internal slots 141 can direct the rack gear150 to take on a conformal curved shape when it travels into this space.

FIG. 9B shows that the housing 40 can be shorter and straight, relativeto the configuration shown in FIG. 9A, for example.

FIGS. 9C, 9F and 9E illustrate a needle tip 30 t to distal end oftubular cannula 20 in a retracted configuration (the needle tip 30 t iscloser to the distal end of the tubular cannula 20 than in an extendedconfiguration/position) with the gear 150 outside the housing 40according to embodiments of the present invention. The gear 150 can beexposed but typically extends and retracts in adjacent tubing 240 (FIG.13) with the inner capillary 31 and/or other needle 30 and/or capillarymember. The needle 30 can travel longitudinally maximally a strokedistance between extended and retracted positions between 1-6 inches,such as between 2-4 inches, while the tubular cannula 20 is fixed in itslength relative to the needle and/or housing 40.

FIG. 9D illustrates a needle tip 30 t to distal end 20 d of the tubularcannula in an extended configuration with the gear 150 totally insidethe housing 40 and its distal end closer to the bottom member 146 b thanin the position shown in FIG. 9E, for example.

FIGS. 9C-9F also illustrate that the fluid transfer assembly 10′ caninclude a tube 65 that encloses the needle 30 and that extends above thehousing 40 to a connector 60, typically a luer connector as discussedabove.

FIGS. 9E and 9F illustrate that the rotatable user interface member 50 ican include a drive shaft 152 that is attached to a center of the pinion151 so that rotation of the member 50 i rotates the pinion 151, whichmoves the rack gear 150 holding the needle 30.

FIGS. 9G, 911 and 9I illustrate exemplary attachment configurations ofcomponents of the assembly 10′. The pin 153 can be affixed, typicallybonded, to the gear 150. The proximal end of the tubular cannula 20 pcan be bonded or otherwise affixed to the distal end of the housing 40d. The gear 150 can be affixed, typically bonded, to the needle 30,typically the inner capillary 31. The needle 30 can extend through andout each end of the gear 150, typically via a longitudinally extendingmedial slot, channel or aperture in the gear 150. The housing members 40a, 40 b can be matably attached, typically bonded, with the gear 150 andneedle 30, typically the inner capillary 31, therein.

The tube 65, attached to the screw 50 s and the needle 30 (i.e., innercapillary 31) can form a unitary assembly so that the screw 50 s, tube65 and needle 30 can move as a unit in the housing 40 to extend andretract the needle tip 30 t.

FIGS. 10A, 10B, 11A and 11B illustrate another embodiment of theassembly 10″. In this embodiment, similar to the embodiment shown inFIG. 1A, the outer wall 40 w of the housing 40 can rotate to engage thelength adjustment mechanism 50″ which can comprise a longitudinallyextending internal screw 50 s. The internal wall can comprise threads 40t that engage the internal screw 50 s so that when a user rotates theouter wall 40 w (i.e., a cylindrical “knob”), the screw 50 s moveslongitudinally up and down. In some embodiments, the screw 50 s isbonded or otherwise affixed to the needle 30 and does not rotate to movethe needle 30 up and down relative to the tubular cannula 20. Thehousing 40 can have upper and lower members 146 u, 146 b that are staticand do not rotate or move in a longitudinal direction. In operation, auser can hold onto one or both of these members 146 u, 146 b and rotatethe intermediate outer wall segment 40 w to move the screw 50 s up ordown and therefore move the needle 30 up or down relative to the tubularcannula 20. A proximal end of the tubular cannula 20 p can terminateinside of and typically at a distal end of the housing 40 d.

Referring to FIG. 11A, the screw 50 s can be held by a hollow internaltubular shaft 156 that can guide the screw 50 s up and down in thehousing 40. The shaft 156 can have a wall 156 w that has an openlongitudinally extending segment 158. The open segment can extendcircumferentially between about 15 to about 90 degrees. The shaft 156can connect/attach to the upper and lower stationary members 146 u, 146b. The longitudinally extending open segment 158 can be a cut out thatis keyed to a matable internal anti-rotation feature. The screw 50 s canhave a radially extending key feature 50 k that can engage a slot in thehousing 40 to provide anti-rotational support.

Referring again to FIG. 11A, the upper and/or lower member 146 u, 146 bcan have user-tactile engagement features 147 such as be knurled, have araised surface pattern and/or have a larger outer dimension or feature(i.e., greater diameter, finger engagement member such as a projectionor fin or body with a larger radial or lateral extent) relative to therotatable cylindrical outer wall segment 40 w that can provide ease ofuser touch and hold during use.

FIGS. 12A-12D also illustrate that the fluid transfer assembly 10″ caninclude a tube 65 that encloses the needle 30 and that extends above thehousing 40 to a connector 60, typically a luer connector as discussedabove.

Referring to FIGS. 12A-12D, the screw 50 s can reside closer to thedistal end of the housing 40 d when the needle tip 30 t is extended,compare, for example, FIGS. 12B-12D with the retracted configurationshown in FIG. 12A.

FIGS. 12E and 12F illustrate exemplary attachment configurations ofcomponents of the assembly 10″. The tube 65 can be attached to an upperend of the screw 50 s and can reside in the support shaft 156. Theopposing ends of the support shaft 156 can be affixed to the respectiveupper and lower members 146 u, 146 b of the housing 40.

Optionally, the needle 30 can travel longitudinally maximally a strokedistance between extended and retracted positions between 1-6 inches,such as between 2-4 inches, while the tubular cannula 20 is fixed in itslength relative to the needle and/or housing 40.

Referring to FIG. 13, in some embodiments, the assembly 10, 10′, 10″ canbe used with a length of flexible (extension) tubing 240 which may beprovided as an integrated subassembly 240 a. In other embodiments, thetubing 240 can be provided as a component separate from the assembly 10,10′, 10″ for assembly prior to or during a procedure. If so, the ends ofthe tubing 240 and/or connectors 60 and 160 may be capped or held insterile sleeves or otherwise package to maintain sterility orcleanliness.

In some embodiments, a length of the needle 30 or a cooperating (fusedsilica) capillary tube 230 can be enchased in the flexible tubing 240.The length may be a short or long length. The flexible tubing 240 canprotect a long length of the proximal end of the needle 30, the lengthabove and outside the housing 40, or another downstream cooperatingneedle and/or capillary 230 attached thereto where such a configurationis used.

In some embodiments, the long needle segment 230 can be one continuouspiece of fused silica glass that goes from the distal end 240 d of thetubing 240 at the connector 160 to the very proximal end 240 p,typically between about 4 feet to about 10 feet long. The tubing 240with the capillary/needle segment 230 can be used to connect the needle30 to the pump P (FIG. 9) or other pressurized source and the deliverysubstance A can flow through the tubing 240 to the needle 30 fordelivery. Further, other MRI compatible needle materials may be used.According to some embodiments, the tubing 240 is flexible PVC tubing.According to some embodiments, the tubing 240 is silicone tubing. Thetubing 240 may have various lengths. For example, in some embodiments,the tubing may be between about four to about ten feet (4 ft-loft) inlength, although other lengths are possible.

The tubular cannula 20 can have a rigid body. The cannula 20 maycomprise alumina/ceramic that can be MRI visible. The cannula 20 canhave an outer surface having a lubricious coating and/or sleeve 23. Thecoating and/or sleeve can be a substantially transparent polymericmaterial. Where a sleeve is used, the sleeve 23 can be a thin flexiblepolymeric sleeve that can be conformably attached to the underlyingcannula body. The coating and/or sleeve can be configured withsufficient strength to be able to retain components of the cannulashould the cannula fracture. The sleeve can be an elastomeric shrinkwrap or tube that can be heat-shrink applied to the underlying body.

The assembly 10, 10′, 10″ can be configured to flowably introduce and/orinject a desired therapy substance (e.g., antigen, gene therapy,chemotherapy or stem-cell or other therapy type).

The connector 160 can be configured as a luer lock to lock to theconnector 60 and the needle/tubing 240/230 can be operatively coupled toan infusion pump P which supplies a mass flow of the desired substanceor material to be delivered into the patient.

As shown in FIGS. 14 and 15, the tubular cannula 20 can extend through atubular support 260 of a trajectory guide 250 t that can be held by abase or frame, e.g., a stereotactic frame that can be secured to thepatient or that can be secured to a holder residing over the patient.See, e.g., U.S. Pat. Nos. 8,315,689, 8,175,677 and 8,374,677 and USPatent Application Publication No. 2010/0198052 (Ser. No. 12/694,865)for descriptions of patient planning and entry protocols and frames andtrajectory guides, the contents of which are hereby incorporated byreference as if recited in full herein.

In some embodiments, the needle 30 is configured to deliver a drugtherapy to the brain. The drug therapy can comprise substance S (FIG.15) delivered to the target site or region A through the tubular cannula20 and cooperating needle 30 may be any suitable and desired substancefor drug discovery, animal or human clinical trials and/or approvedmedical procedures. According to some embodiments, the substance S is aliquid or slurry. In the case of a tumor, the substance may be achemotherapeutic (cytotoxic) fluid. In some embodiments, the substancecan include certain types of advantageous cells that act as vaccines orother medicaments (for example, antigen presenting cells such asdentritic cells). The dentritic cells may be pulsed with one or moreantigens and/or with RNA encoding one or more antigen. Exemplaryantigens are tumor-specific or pathogen-specific antigens. Examples oftumor-specific antigens include, but are not limited to, antigens fromtumors such as renal cell tumors, melanoma, leukemia, myeloma, breastcancer, prostate cancer, ovarian cancer, lung cancer and bladder cancer.Examples of pathogen-specific antigens include, but are not limited to,antigens specific for HIV or HCV. In some embodiments, the substance Smay comprise radioactive material such as radioactive seeds. SubstancesS delivered to a target area in accordance with embodiments of thepresent invention may include, but are not limited to, the followingdrugs (including any combinations thereof) listed in Table 1:

TABLE 1 DRUG (generic name) DISORDER(S) Caprylidene Alzheimer's diseaseDonepezil Alzheimer's disease Galantamine Alzheimer's disease MemantineAlzheimer's disease Tacrine Alzheimer's disease vitamin E Alzheimer'sdisease ergoloid mesylates Alzheimer's disease Riluzole Amyotrophiclateral sclerosis Metoprolol Benign essential tremors Primidone Benignessential tremors Propanolol Benign essential tremors Gabapentin Benignessential tremors & Epilepsy Nadolol Benign essential tremors &Parkinson's disease Zonisamide Benign essential tremors & Parkinson'sdisease Carmustine Brain tumor Lomustine Brain tumor Methotrexate Braintumor Cisplatin Brain tumor & Neuroblastoma Ioversol Cerebralarteriography Mannitol Cerebral Edema Dexamethasone Cerebral Edema &Neurosarcoidosis Baclofen Cerebral spasticity Ticlopidine Cerebralthrombosis/embolism Isoxsuprine Cerebrovascular insufficiency CefotaximeCNS infection & Meningitis Acyclovir Encephalitis Foscarnet EncephalitisGanciclovir Encephalitis interferon alpha-2a Encephalitis CarbamazepineEpilepsy Clonazepam Epilepsy Diazepam Epilepsy divalproex sodiumEpilepsy Ethosuximide Epilepsy Ethotoin Epilepsy Felbamate EpilepsyFosphenytoin Epilepsy Levetiracetam Epilepsy Mephobarbital EpilepsyParamethadione Epilepsy Phenytoin Epilepsy Trimethadione EpilepsyPregabalin Epilepsy & Neuralgia immune globulin intravenousGuillain-Barre Syndrome interferon beta-1b Guillain-Barre Syndrome &Multiple sclerosis Azathioprine Guillain-Barre Syndrome & Multiplesclerosis & Neurosarcoidosis Risperidone Head injury TetrabenazineHuntington's disease Acetazolamide Hydrocephalus & Epilepsy AlteplaseIschemic stroke Clopidogrel Ischemic stroke Nimodipine Ischemic stroke &Subarachnoid hemorrhage Aspirin Ischemic stroke & Thromboembolic strokeAmikacin Encaphalitis Ampicillin Encaphalitis ampicillin/sulbactamEncaphalitis Ceftazidime Encaphalitis Ceftizoxime EncaphalitisCefuroxime Encaphalitis Chloramphenicol Encaphalitis cilastatin/imipenemEncaphalitis Gentamicin Encaphalitis Meropenem EncaphalitisMetronidazole Encaphalitis Nafcillin Encaphalitis Oxacillin EncaphalitisPiperacillin Encaphalitis Rifampin Encaphalitissulfamethoxazole/trimethoprim Encaphalitis Tobramycin EncaphalitisTriamcinolone Encaphalitis Vancomycin Encaphalitis CeftriaxoneEncaphalitis & Neurosyphilis Penicillin Encaphalitis & NeurosyphilisCorticotrophin Multiple sclerosis Dalfampridine Multiple sclerosisGlatiramer Multiple sclerosis Mitoxantrone Multiple sclerosisNatalizumab Multiple sclerosis Modafinil Multiple sclerosisCyclophosphamide Multiple sclerosis & Brain tumor & Neuroblastomainterferon beta-1a Multiple sclerosis & Neuritis Prednisolone Multiplesclerosis & Neurosarcoidosis Prednisone Multiple sclerosis &Neurosarcoidosis Amantadine Multiple sclerosis & Parkinson's diseaseMethylprednisolone Neuralgia Desvenlafaxine Neuralgia NortriptylineNeuralgia Doxorubicin Neuroblastoma Vincristine NeuroblastomaAlbendazole Neurocystecercosis chloroquine phosphate NeurosarcoidosisHydroxychloroquine Neurosarcoidosis Infliximab NeurosarcoidosisPentoxyfilline Neurosarcoidosis Thalidomide Neurosarcoidosis ApomorphineParkinson's disease Belladonna Parkinson's disease BenztropineParkinson's disease Biperiden Parkinson's disease BromocriptineParkinson's disease Carbidopa Parkinson's diseasecarbidopa/entacapone/levodopa Parkinson's disease carbidopa/levodopaParkinson's disease Entacapone Parkinson's disease Levodopa Parkinson'sdisease pergolide mesylate Parkinson's disease Pramipexole Parkinson'sdisease Procyclidine Parkinson's disease Rasagiline Parkinson's diseaseRopinirole Parkinson's disease Rotiotine Parkinson's disease ScopolamineParkinson's disease Tolcapone Parkinson's disease TrihexyphenidylParkinson's disease Seleginline Parkinson's disease RivastigmineParkinson's disease & Alzheimer's disease Anisindione Thromboembolicstroke Warfarin Thromboembolic stroke 5-hydroxytryptophan Depression &Anxiety & ADHD Duloxetine Depression & Anxiety & Bipolar disorderEscitalopram Depression & Anxiety & Bipolar disorder VenlafaxineDepression & Anxiety & Bipolar disorder & Autism & Social anxietydisorder Desvenlafaxine Depression & Anxiety & PTSD & ADHD ParoxetineDepression & Anxiety & PTSD & Social anxiety disorderfluoxetine/olanzapine Depression & Bipolar disorder 1-methylfolateDepression & BPD Amitriptyline Depression & PTSD Sertraline Depression &PTSD & Bipolar disorder & Social anxiety disorder Fluvoxamine Depression& PTSD & Social anxiety disorder Olanzapine Depression & Schizophrenia &Bipolar disorder Paliperidone Depression & Schizophrenia & Bipolardisorder Aripiprazole Depression & Schizophrenia & Bipolar disorder &Autism Quetiapine Depression & Schizophrenia & PTSD & BPD & Bipolardisorder Risperidone Depression & Schizophrenia & PTSD & BPD & Bipolardisorder & Autism Amisulpride Depression & Social anxiety disorderChlorpromazine Psychosis Droperidol Psychosis Fluphenazine PsychosisPericiazine Psychosis Perphenazine Psychosis Thiothixene PsychosisTriflupromazine Psychosis Haloperidol Psychosis & Dementia Prazosin PTSDClozapine Schizophrenia Flupenthixol Schizophrenia IloperidoneSchizophrenia Loxapine Schizophrenia Mesoridazine SchizophreniaPromazine Schizophrenia Reserpine Schizophrenia ThioridazeinSchizophrenia Zuclopenthixol Schizophrenia Asenapine Schizophrenia &Bipolar disorder Levomepromazine Schizophrenia & Bipolar disorderZiprasidone Schizophrenia & Bipolar disorder Molindone Schizophrenia &Psychosis Pimozide Schizophrenia & Psychosis Thioridazine Schizophrenia& Psychosis Cytarabine Chemotherapy, hematological malignancies

According to some embodiments, the assembly 10, 10′, 10″ is configuredas an infusate delivery system that is delivered to a patient at aninfusion rate in the range of from about 1 to 3 μL/minute.

Insertion of the surgical tubular cannula 20 (or any other surgical,e.g., delivery, cannula) can be tracked in near real time by referenceto a void in the patient tissue caused by the cannula 20 and reflectedin the MR image. In some embodiments, one or more MRI-visible fiducialmarkers may be provided on the surgical cannula 20 or housing 40, MRscanned and processed, and displayed on the UI. In some embodiments, thesurgical cannula 20 may itself be formed of an MRI-visible material, MRscanned and processed, and displayed on the UI.

According to some embodiments, the surgical cannula 20 may include anembedded intrabody MRI antenna that is configured to pick-up MM signalsin local tissue during an MRI procedure. The MRI antenna can beconfigured to reside on a distal end portion of the surgical cannula. Insome embodiments, the antenna has a focal length or signal-receivinglength of between about 1-5 cm, and typically is configured to have aviewing length to receive MM signals from local tissue of between about1-2.5 cm. The MRI antenna can be formed as comprising a coaxial and/ortriaxial antenna. However, other antenna configurations can be used,such as, for example, a whip antenna, a coil antenna, a looplessantenna, and/or a looped antenna. See, e.g., U.S. Pat. Nos. 5,699,801;5,928,145; 6,263,229; 6,606,513; 6,628,980; 6,284,971; 6,675,033; and6,701,176, the contents of which are hereby incorporated by reference asif recited in full herein. See also U.S. Patent Application PublicationNos. 2003/0050557; 2004/0046557; and 2003/0028095, the contents of whichare also hereby incorporated by reference as if recited in full herein.

While the surgical cannula 20 and needle 30 have been described by wayof example as delivery devices and methods for delivering a substance toa patient, in accordance with some embodiments of the invention, thecannula 20 and needle 30 and associated methods can be used to withdrawa substance (e.g., spinal fluid, cardiac fluid or neuro fluid) from apatient. Thus, it will be appreciated that the devices and methods asdisclosed herein can be used to transfer a substance into and/or from apatient.

While the devices have been described herein primarily with reference toMRI-guided insertion and infusion procedures, in some embodiments thedevices can be used in procedures without MRI guidance.

While the surgical tubular cannula 20 has been described in use with atrajectory guide 250 t, the cannula 20 may be used with other types oftrajectory guidance or stereotactic frames or without a stereotacticframe or trajectory guide.

FIG. 14 illustrates an MRI-guided interventional system 100 with an MRIscanner 1220, a clinician workstation 1230 with at least one circuit1230 c, at least one display 1232, an MRI compatible trajectory guide250 t and a fluid transfer assembly 300 (including the assembly 10, 10′,10″ and tubing 240 (FIG. 13). In some embodiments, the fluid exchange(i.e., delivery) assembly 300 can cooperate with an automated infusionpump P or, less preferably, a manual syringe, or another pressurizeddelivery source.

The system 100 can be configured to render or generate near real time orreal time visualizations of the target anatomical space using MRI imagedata and predefined data of at least one surgical tool (e.g., tubularcannula 20, housing 40 and/or trajectory guide 250 t) to segment theimage data and place the trajectory guide 250 t and the cannula 20 inthe rendered visualization in the correct orientation and position in 3Dspace (which is the MRI surgical space for MM embodiments), anatomicallyregistered to a patient. The trajectory guide 250 t and the cannula 20can include or cooperate with tracking, monitoring and/or otherinterventional components.

An exemplary trajectory guide 250 t is illustrated in FIG. 14 in anexemplary (head) position on a patient. However, the trajectory guidecan be used for any target location including, for example, the spine.The trajectory guide 250 t can be mounted over or on an object, e.g.,patient or subject, so that the upper receiving tube/support column 260(FIG. 15) is oriented substantially perpendicular to the entry location(typically for spinal uses) or may be mounted to extend outward from thepatient entry location at an angle as shown in FIG. 14.

The trajectory guide 250 t typically provides X-Y adjustment and pitchand roll adjustment in order to accurately position the cannula 20 at adesired location within a patient. For additional discussion of examplesof suitable trajectory guides, see U.S. Pat. No. 8,374,677, the contentsof which are hereby incorporated by reference as if recited in fullherein. However, it is noted that other trajectory guide configurationsmay be used and embodiments of the invention are not limited by theexamples of the trajectory guides herein.

According to some embodiments, the systems are configured to provide asubstantially automated or semi-automated and relatively easy-to-useMRI-guided system with defined workflow steps and interactivevisualizations. In particular embodiments, the systems define andpresent workflow with discrete steps for finding target and entrypoint(s), guiding the alignment of the targeting cannula to a plannedtrajectory, monitoring the insertion of the tubular (guide) cannula 20,and adjusting the (X-Y) position in cases where the placement needs tobe corrected. During steps where specific MR scans are used, the circuitor computer module can display data for scan plane center and angulationto be entered at the console. The workstation/circuit can passively oractively communicate with the MR scanner. The system can also beconfigured to use functional patient data (e.g., fiber tracks, fMRI andthe like) to help plan or refine a target surgical site and/or accesspath.

The system 100 may also include a decoupling/tuning circuit that allowsthe system to cooperate with an MRI scanner 1220 and filters and thelike. See, e.g., U.S. Pat. Nos. 6,701,176; 6,904,307 and U.S. PatentApplication Publication No. 2003/0050557, the contents of which arehereby incorporated by reference as if recited in full herein.

FIG. 16 is a flow chart of exemplary actions that can be carried outaccording to embodiments of the present invention. A housing holding atubular cannula with an elongate needle extending through the tubularcannula is provided so that a needle tip is external to the tubularcannula (block 400). A screw or gear in the housing is rotated tolongitudinally translate the tubular cannula and/or the needle tip outof the housing (block 410). Adjusting, in vivo, a distance between thedistal end of the tubular cannula and the needle tip based on thelongitudinal translation (block 420).

The housing can be attached to a length of tubing encasing a length ofcapillary tubing forming part of the needle that extends outside thehousing that extends to a connector, the method includes connecting theconnector to another connector holding fused silica capillary tubinginside a length of flexible tubing that is in fluid communication with apump (block 430).

A full stroke of translation can be between 0.5 inches and 2 inches orabout 1.6 inches, such as about 1.25 inches (block 440).

The needle can have a tip defined by an inner capillary tube and can befixedly attached to an outer capillary tube that defines an increasedouter wall segment a distance of 1-5 mm, typically 3 mm from the tip(block 445).

Inserting the tubular cannula into a trajectory guide mounted to apatient and rotating the screw while the tubular cannula held in thetrajectory guide (block 450).

The rotating can be carried out by rotating an outer wall of the housingto rotate the screw (block 455).

The screw can be or gear can comprise a longitudinally extending screwattached to an outerwall of the tubular cannula and the housing has aninner wall segment with internal threads that engage the screw attachedto the tubular cannula to cause the translation (block 460).

The screw or gear can comprise a longitudinally extending rack gear thatis attached to the needle and that can move the needle relative to thetubular cannula in response to rotation of an external thumb wheel thatrotates a pinion that engages the rack gear (block 462).

The cannula and needle can be an infusate ventricular delivery systemfor brain delivery of a target substance to a target anatomical region(block 465). For example, the device can be configured to allow a singleintrabody insertion of the needle 30 to a target anatomical region inthe brain (such as tissue generally in-line with and between the noseand back of the head and, starting dispensing/infusing from the back ofthe head while translating the needle frontward to treat a large volumethrough one intrabody insertion of the needle).

The foregoing is illustrative of the present invention and is not to beconstrued as limiting thereof. Although a few exemplary embodiments ofthis invention have been described, those skilled in the art willreadily appreciate that many modifications are possible in the exemplaryembodiments without materially departing from the teachings andadvantages of this invention. Accordingly, all such modifications areintended to be included within the scope of this invention as defined inthe claims. The invention is defined by the following claims, withequivalents of the claims to be included therein.

That which is claimed is:
 1. A surgical assembly for transferring fluidto or from a subject, comprising: a tubular cannula having opposingproximal and distal ends with an open axially extending lumen; anelongate needle having opposing proximal and distal ends, wherein alength of the needle extends through the tubular cannula lumen so thatthe distal end of the needle with a tip extends out of the distal end ofthe distal end of the tubular cannula to provide an exposed needle tip;and a housing comprising opposing proximal and distal ends, wherein thehousing holds the tubular cannula with the needle with the tubularcannula and needle extending out of the distal end of the housing,wherein the housing comprises an internal length adjustment mechanismthat is attached to one or both of the tubular cannula or the needle andthat adjusts a length between the distal end of the tubular cannula andthe exposed needle tip, wherein the elongate needle comprises a tubethat extends through the housing and the tubular cannula and defines theexposed needle tip, wherein the tube of the elongate needle comprises acontinuous length of fused silica glass that extends out of bothproximal and distal ends of the housing, wherein the distal end of theneedle has a stepped configuration with a first segment having a firstouter diameter that merges into a second end segment having a secondsmaller outer diameter having a length that extends to the tip of theneedle, and wherein the needle tip extends out of the tubular cannula anadjustable distance of between about 2 mm to about 30 mm.
 2. Theassembly of claim 1, wherein the housing has a length from about 1 inchto about 6 inches and comprises an external rotatable member or arotatable cylindrical outer wall that engages the length adjustmentmechanism to move at least one of the needle or the tubular cannulalongitudinally.
 3. The assembly of claim 1, wherein the housingcomprises an external thumbwheel that engages an internal gear of thelength adjustment mechanism and that is attached to the tubular cannulaor the needle to longitudinally move the tubular cannula or the needleto adjust the length, and wherein the tubular cannula is an outertubular cannula with a tapered distal end portion, and wherein theexposed needle tip is configured to always be outside of the tubularcannula.
 4. The assembly of claim 1, wherein the length adjustmentmechanism comprises an internal screw, and wherein the housing comprisesa rotatable outer wall, and wherein, in response to rotation of theouter wall of the housing, the internal screw longitudinally translatesto adjust the length between the distal end of the tubular cannula andthe exposed tip of the needle.
 5. The assembly of claim 4, wherein theneedle has a stroke distance of between about 0.5 inches and 3 inchesand has a proximal end that extends a length outside a proximal end ofthe housing.
 6. The assembly of claim 1, wherein the housing holds alongitudinally extending screw of the length adjustment mechanism in thehousing that is in communication with the rotatable outer wall that canmove longitudinally in response to the rotation of the outer wall toadjust the length between the distal end of the tubular cannula and theneedle tip.
 7. The assembly of claim 1, wherein the tube extends adistance above the proximal end of the housing and through the housingto define the exposed needle tip, the assembly further comprising a luerconnector attached to the tube above the proximal end of the housing. 8.The assembly of claim 1, wherein the tubular cannula has an outerpolymeric coating and/or sleeve, wherein a distal end of the tubularcannula is tapered so that it has a smaller outer diameter at a tip ofthe tubular cannula relative to an outer diameter rearward of the tip ofthe tubular cannula, and wherein a proximal end of the tubular cannulaterminates inside the housing.
 9. The assembly of claim 1, wherein anouter surface of the tubular cannula has a size and geometry adapted foruse with a stereotactic frame with a trajectory guide having a supportcolumn sized and configured to releasably hold the tubular cannula sothat the housing resides above the support column, and wherein theneedle has an inner diameter of between about 100 μm to about 750 μm.10. A surgical assembly for transferring fluid to or from a subject,comprising: a tubular cannula having opposing proximal and distal endswith an open axially extending lumen; an elongate needle having opposingproximal and distal ends, wherein a length of the needle extends throughthe tubular cannula lumen so that the distal end of the needle with atip extends out of the distal end of the distal end of the tubularcannula to provide an exposed needle tip; a housing comprising opposingproximal and distal ends, wherein the housing holds the tubular cannulawith the needle with the tubular cannula and needle extending out of thedistal end of the housing, wherein the housing comprises an internallength adjustment mechanism that is attached to one or both of thetubular cannula or the needle and that adjusts a length between thedistal end of the tubular cannula and the exposed needle tip; whereinthe elongate needle comprises a tube that extends through the housingand the tubular cannula and defines the exposed needle tip, and whereinthe tube extends a distance above the proximal end of the housing: aluer connector attached to the tube above the proximal end of thehousing; and flexible tubing encasing the tube above the housing,attached to a proximal end of the housing and the luer connector.
 11. Asurgical assembly for transferring fluid to or from a subject,comprising: a tubular cannula having opposing proximal and distal endswith an open axially extending lumen; an elongate needle having opposingproximal and distal ends, wherein a length of the needle extends throughthe tubular cannula lumen so that the distal end of the needle with atip extends out of the distal end of the distal end of the tubularcannula to provide an exposed needle tip; and a housing comprisingopposing proximal and distal ends, wherein the housing holds the tubularcannula with the needle with the tubular cannula and needle extendingout of the distal end of the housing, wherein the housing comprises aninternal length adjustment mechanism that is attached to one or both ofthe tubular cannula or the needle and that adjusts a length between thedistal end of the tubular cannula and the exposed needle tip, wherein adistal end of the tubular cannula is tapered so that it has a smallerouter diameter at a tip of the tubular cannula relative to an outerdiameter rearward of the tip of the tubular cannula, and wherein aproximal end of the tubular cannula terminates inside the housing,wherein the elongate needle comprises a tube that extends through thehousing and the tubular cannula and defines the exposed needle tip, andwherein the tubular cannula comprises a ceramic material and a conformalouter polymeric sleeve, wherein the tube is an inner tube that is bondedto an outer tube over a longitudinally extending length inside thehousing and tubular cannula and a length that can be external to thetubular cannula that define at least first and second co-axiallydisposed external segments having different outer diameters, with asmallest sized outer diameter of the first segment extending to theneedle tip, and wherein the outer tube comprises a conformal outerpolymeric sleeve residing at least at an interface between the distalend of the tubular cannula and the outer tube to contact an innersurface of the tubular cannula when retracted therein to thereby inhibitfluid intake thereat.
 12. The assembly of claim 11, wherein the outertube terminates inside the housing while the inner tube extends out ofthe housing proximal end.
 13. A surgical assembly for transferring fluidto or from a subject, comprising: a tubular cannula having opposingproximal and distal ends with an open axially extending lumen; anelongate needle having opposing proximal and distal ends, wherein alength of the needle extends through the tubular cannula lumen so thatthe distal end of the needle with a tip extends out of the distal end ofthe distal end of the tubular cannula to provide an exposed needle tip;and a housing comprising opposing proximal and distal ends, wherein thehousing holds the tubular cannula with the needle with the tubularcannula and needle extending out of the distal end of the housing,wherein the housing comprises an internal length adjustment mechanismthat is attached to one or both of the tubular cannula or the needlethat adjusts a length between the distal end of the tubular cannula andthe exposed tip of the needle, wherein the length adjustment mechanismcomprises a flexible rack gear that is configured to longitudinallyreciprocate relative to the housing and at least partially extend out ofthe housing and retract into the housing to adjust the length, whereinthe flexible rack gear has sufficient rigidity to have a self-supportingthree dimensional shape but flexes from a straight longitudinallyextending orientation inside the housing to a curvilinear orientationwhen outside the housing, and wherein the needle is coupled to andextends through the flexible rack gear to extend out of opposingproximal and distal ends of the flexible rack gear.
 14. A surgicalassembly for intrabody fluid transfer, comprising: a tubular cannulahaving opposing proximal and distal ends with an open axially extendinglumen, wherein a distal end portion of the tubular cannula is tapered sothat it has a smaller outer diameter at a tip of the tubular memberrelative to an outer diameter of the tubular member closer to thehousing; an elongate needle having opposing proximal and distal ends,wherein a length of the needle extends through the tubular cannula lumenso that the distal end of the needle with a tip extends out of thedistal end of the distal end of the tubular cannula to provide anexposed needle tip, wherein the exposed needle tip is configured toalways remain outside the tip of the tubular cannula; a housingcomprising opposing proximal and distal ends and a rotatable externalmember or a rotatable outer wall that holds the tubular cannula with theneedle with the tubular cannula and needle extending out of the distalend of the housing; and a length adjustment mechanism in communicationwith the rotatable external member or the rotatable outer wall thatmoves the needle or the tubular cannula longitudinally to extend andretract the distal end of the needle relative to the tubular cannula,wherein the rotatable external member or the rotatable outer wall isconfigured to cooperate with the length adjustment mechanism to adjust alength between the distal end of the tubular cannula and the exposed tipof the needle, wherein the length adjustment mechanism comprises aflexible rack gear that extends in a longitudinal direction in thehousing and that has sufficient rigidity to have a self-supporting threedimensional shape but that can flex-when outside the housing, whereinthe flexible rack gear is configured to longitudinally reciprocaterelative to the housing, and wherein the needle is coupled to andextends through and out of opposing proximal and distal ends of theflexible rack gear.
 15. The assembly of claim 14, wherein the lengthadjustment mechanism comprises a pinion gear in communication with therotatable external member and a longitudinally extending rack gear thatengages the pinion gear that moves the needle or the tubular cannulalongitudinally without rotation of the needle or the tubular cannula.16. The assembly of claim 14, wherein the needle comprises an inner tubethat extends a distance above the proximal end of the housing andthrough the housing to the needle tip to define the needle tip, theassembly further comprising a luer connector attached to the inner tubeabove the proximal end of the housing.
 17. A method of transferring asubstance to and/or from a patient, the method comprising: providing ahousing having opposing proximal and distal ends, the housing holding aproximal end of a tubular cannula therein with a distal end of thetubular cannula extending out of the housing, the tubular cannula havingan axially extending interior lumen holding an elongate needle with alength sufficient to have a tip of the needle outside the distal end ofthe tubular cannula and an upper end extending out of the proximal endof the housing; inserting the distal end of the tubular cannula andneedle into a patient; then transferring a substance to or from a targetsite through a needle lumen at the tip of the needle; adjusting a lengthbetween the distal end of the tubular cannula and needle tip during thetransferring action; and wherein the adjusting the length is carried outusing a length adjustment mechanism comprising a flexible rack gearfixedly attached to a sub-length of the needle above the distal end ofthe housing, and wherein the needle extends through the flexible rackgear and extends out of opposing proximal and distal ends of theflexible rack gear.
 18. The method of claim 17, wherein the needle is aninfusion needle, and wherein the transferring the substance to or fromthe target site is carried out by infusing a substance.
 19. The methodof claim 17, wherein the target site is the brain, and wherein theinserting, transferring and adjusting steps are carried out while thepatient is in a magnetic field of an MRI Scanner, wherein the rack gearis held in a straight longitudinally extending orientation when insidethe housing, and wherein the method comprises bending the rack gear up,down or side-side when outside the housing, and inside a bore of the MRIScanner.
 20. The method of claim 17, wherein the adjusting is carriedout by extending the needle a distance out of a distal end of thetubular cannula while the tubular cannula is held at a fixed length byrotating an outer wall of the housing.
 21. The method of claim 17,wherein the adjusting is carried out by extending the needle a distanceout of a distal end of the tubular cannula while the tubular cannula isheld at a fixed length by rotating an outer thumbwheel to rotate apinion gear to longitudinally translate rack gear held at leastpartially inside the housing with the rack gear fixedly attached to theneedle.
 22. The method of claim 17, wherein the rack gear is held in astraight longitudinally extending orientation when inside the housing,and wherein the method comprises bending the rack gear up, down orside-side when exposed to the environment outside the housing whileholding a length of the needle in the rack gear during the adjustingstep.
 23. A surgical assembly for intrabody fluid transfer, comprising:a tubular cannula having opposing proximal and distal ends with an openaxially extending lumen; an elongate needle having opposing proximal anddistal ends, wherein a length of the needle extends through the tubularcannula so that the distal end of the needle extends out of the distalend of the tubular cannula to provide an exposed needle tip; a housingcomprising opposing proximal and distal ends and a rotatable externalmember or a rotatable outer wall that holds the tubular cannula with thetubular cannula and needle extending out of the distal end of thehousing; a length adjustment mechanism in communication with therotatable external member or the rotatable outer wall that moves atleast one of the needle or the tubular cannula longitudinally to extendand retract the distal end of the needle relative to the tubular cannulato adjust a length between the distal end of the tubular cannula and theexposed tip of the needle; wherein the needle is defined by an innertube bonded to an outer tube to define at least first and secondco-axially disposed segments having different outer diameters, with theinner tube being longer than the outer tube and defining the exposedneedle tip; and wherein the inner tube is directly affixed to theinternal length adjustment mechanism.
 24. The surgical assembly of claim23, wherein the length adjustment mechanism comprising a longitudinallyextending flexible rack gear with longitudinally spaced apart andlaterally extending gear teeth extending across an entire widthdimension of the flexible rack gear, and wherein the inner tube extendslongitudinally through a medial portion of the body of the rack gear andextends out of opposing proximal and distal ends of the flexible rackgear.